Inclusion Criteria:

Patients are eligible to be included in the study only if they meet all of the following criteria:

1. Patients with completely resected stage IB (> 4 cm), II, or IIIA NSCLC. Patient must be enrolled and begin therapy within 4 to 12 weeks from the date of complete surgical resection.
2. Fresh tissue must be available for genomics expression profiling.
3. ECOG performance status of 0 or 1.
4. NO prior chemotherapy, radiation therapy, or biologic/targeted therapy within the last 5 years. Prior therapy with low dose methotrexate or similar medications is allowed if therapy used to treat non-malignant conditions.
5. Age ≥ 18 years.
6. No previous or concomitant malignancy in the past 5 years other than curatively-treated carcinoma in situ of the cervix, or basal cell or squamous cell carcinoma of the skin.
7. No other serious medical or psychiatric illness.
8. Signed informed consent.

9. Required laboratory data within one week of enrollment:

   • ANC or AGC ≥ 1500 per uL;
   • Platelets ≥ 100,000 per uL;
   • Total bilirubin ≤ 1.5 mg/dL;
   • Creatinine < 2 mg/dL; creatinine clearance ≥ 45 mL/min;
   • SGOT/SGPT ≤ 1.5x ULN.
10. Females of child-bearing potential (not surgically sterilized and between menarche and 1 year post menopause) must test negative for pregnancy within 7 days prior to or at the time of enrollment based on a serum pregnancy test. Both sexually active males and females of reproductive potential must agree to use a reliable method of birth control, as determined by the patient and their health care team, during the study and for 3 months following the last dose of study drug.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

1. Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
2. Concurrent administration of any other anti-tumor therapy (see #4 inclusion for exceptions).
3. Inability to comply with protocol or study procedures.
4. Active infection requiring IV antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
5. Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant systemic disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
6. Myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications.
7. Contraindication to corticosteroids.
8. Inability or unwillingness to take folic acid or vitamin B12 supplementation.
9. Unwillingness to stop taking herbal supplements while on study.
10. Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry and throughout study enrollment as the distribution of pemetrexed in this fluid space is not fully understood.
11. Inability to discontinue administration of aspirin at a dose > 1300 mg/day or other long acting, non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam). Moderate dose ibuprofen may be continued.
12. Female patients that are pregnant or breast-feeding.